OBJECTIVE: To investigate the characteristics of sulfation of scutellarein in FVB/NCrIVr (FVB) mice. METHODS: FVB mouse intestinal perfusion model and incubation system with FVB mouse liver S9 fractions were adapted to conduct the study. HPLC-MS/MS and HPLC-UV were used to identify and quantify scutellarein and its metabolites in the samples. RESULTS: One sulfation metabolite and one glucuronidation metabolite were detected in the small intestinal perfusate. There was no significant difference between the excretion rates of sulfation metabolite and glucuronidation metabolite in small intestinal perfusate (P=0.435), while only sulfation metabolite of scutellarein could be detected in colon perfusate, scutellarein, sulfation metabolite and glucuronidation metabolite of scutellarein could all be detected in biliary samples, indicating an entero-hepatic circulation of scutellarein. In the liver S9 fractions, sulfation rate at 20 μmol·L-1 was sig nificantly higher than those at 10 and 40 μmol·L-1 (P<0.05). CONCLUSION: Sulfation was found to be the most important metabolism route in the intestinal disposition of scutellarein. There is probably a substrate inhibition effect in the sulfation of scutellarein in liver S9 fractions.

ObjectiveTo compare the clinical results of small surgical incision of bilateral spinous process and traditional open surgical incision in posterior single level lumbar interbody fusion,and assess the application value of the small surgical incision of bilateral spinous process in posterior single level lumbar interbody fusion.MethodsFrom December 2006 to June 2008,70 patients with lower lumbar vertebral diseases underwent single segment posterior lumbar interbody fusion.Patients were randomly divided into small surgical incision of bilateral spinous process group(Hereinafter referred to as small incision group) of 36 cases and 34 cases of conventional open group.Small incision group included 20 males and 16 females with an average age of 52.0 years.Traditional open group included 16 males and 18 females with an average age of 53.2 years.Two groups of operative time,blood loss,postoperative drainage,X-ray projection operation frequency,hospital stay,complication rate,creatine phosphokinase (CPK) level,multifidus cross-sectional area,postoperative low back pain visual analogue scale(VAS),Oswestry disability index(ODI),interbody fusion rate were compared,respectively.ResultsAll of 70 cases were followed up for 12-24 months (average,16).There were no statistically differences in the operation time,the number of X-ray projection,complication rate,and fusion rate between the two groups (P＞0.05),but there were significant differences in blood loss,postoperative drainage,the first day and the third day of postoperative the level of CPK,postoperative multifidus muscle cross-sectional area,postoperative low back pain VAS,hospital stay,and postoperative ODI between the two groups(P＜0.05).ConclusionSmall surgical incision of bilateral spinous process and traditional open surgical posterior lumbar interbody fusion were satisfied with the efficacy,but small surgical incision of bilateral spinous process with less trauma,shorter hospital stay,and rapid postoperative recovery.

OBJECTIVETo explore various factors affecting the clinical pregnancy outcomes of artificial insemination with donor sperm (AID).

METHODSWe retrospectively analyzed 15,744 cycles of AID in 6302 women and investigated the association of the clinical pregnancy outcomes of AID with the treatment protocols, the times of insemination per cycle, the age of the infertile women, the status of the oviduct, and the number of AID cycles.

RESULTSThe pregnancy rate of AID was higher in the chlomiphene-treated women than in those of the natural cycle group (P = 0.003) but showed no significant differences either between the chloramiphene and human menopause gonadotropin (HMG) or between the HMG and natural cycle groups (P > 0.05), and so was it in the women that had received AID twice per cycle before and after ovulation (26.3%) than in those that had undergone only once before (7.0%) or after ovulation (23.7%) (P < 0.05). However, the pregnancy rate was remarkably lower in the women aged 35-40 years (16.5%), especially in those over 40 years (1.2%), than in those under 35 years (26.0%) (P < 0.05). There was no significant difference in the success rate of AID between the women with oviductal adhesion and those without (27.4% vs. 28.1%, P > 0.05). The pregnancy rate of the first cycle of AID (27.6%) was markedly higher than those of the second (24.7%), third (23.9%), and fourth (23.1%) (P < 0.01), but with no significant differences among the latter three cycles (P > 0.05), while that of the fifth cycle (19.0%) was remarkably lower than those of the first four (P < 0.01).

CONCLUSIONThe age of the infertile women is an important factor affecting the success rate of AID. AID twice per cycle is better than once only. For those without oviductal factors, at least 4 cycles of AID are required before in vitro fertilization.

Adult ; Age Factors ; Female ; Fertilization in Vitro ; Humans ; Infertility, Female ; Insemination, Artificial ; Insemination, Artificial, Heterologous ; Ovulation ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies

Objective To evaluate the value of diffusion weighted imaging in differential diagnosis of endometrial carcinoma stagedⅠa.Methods A retrospective analysis of 18 patients with endometrial carcinoma staged Ⅰ a which was confirmed by pathology. Other 22 patients with benign endometrial diseases were also enrolled in the study including endometrial hyperplasia in 9,endometrial polyp in 8 and degenerative submucous myoma in 5.DWI with b value of 0 s/mm2 and 1 000 s/mm2 was performed with single shot sequence of EPI,and the ADC values were measured.Results The mean ADC values of endometrial carcinoma staged Ⅰa,endome-trial hyperplasia,endometrial polyp and degenerative submucous myoma were (0.89±0.21)×10 -3 mm2/s,(1.45±0.19)×10 -3 mm2/s, (1.29±0.32)×10 -3 mm2/s and (1.32 ±0.29)× 10 -3 mm2/s,respectively.There were statistical significant differences between them (F =48.021,P =0.00).Furthermore,statistically significant differences also existed between endometrial carcinoma and other groups (P <0.05).Conclusion ADC value shows a good value in differential diagnosis of endometrial carcinoma staged Ⅰa.

Objective:To investigate the effect of silver diamine fluoride(SDF)on the bonding strength between dentine and glass ion-omer cement(GIC).Methods:1 2 extracted sound molars were prepared into dintine samples and distributed into sound dentine group and demineralized dentine group.According to the treatment methods,the samples in each group were respectively divided into 3 sub-groups:A(control group),B[coated with 38% Ag(NH3 )F2 ]and C(SDF treatment with additional lighting-curing)(n =20).Then a hand-mixed conventional glass ionomer cement Fuji IX was placed on the dentine surface.After 24 h,micro tensile bond strength test and scanning electron microscope (SEM)analysis were conducted.Results:The bonding strength of demineralized dentine was higher than that of sound dentine(P <0.01 ).SDF with additional lighting-curing treated dentine showed a higer bonding strength value than only SDF treated dentin(P <0.01 ).Conclusion:SDF may improve the bonding between dentine and GIC.

Objective:To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit,bleeding risk and platelet aggregation in very elderly patients. Methods:Arachidonic acid induced platelet aggregation(AA-Ag)was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d).In the study,100 patients with low on-treatment platelet ag-gregation and at high risk of bleeding and low risk of cardiovascular events,were switched to aspirin (40 mg/d)and their platelet aggregation was measured again 7 days later.Their bleeding and upper gastroin-testinal symptoms were also recorded in following 3 months.Results:The study observed a heterogeneous distributed aspirin 100 mg/d AA-Ag (range:0.42% to 28.78%)in the 537 very elderly patients.Aspi-rin 100 mg/d AA-Ag before the switch in aspirin 40 mg/d group was 5.00% ±2.32% and the rate of the patients with low on-treatment platelet aggregation was 71.00%.The rates of melena or occult blood positive,other minimal bleeding,upper gastrointestinal symptoms and a history of gastrointestinal bleeding in 40 mg/d group were higher than those in 100 mg/d group.On a regimen of aspirin 40 mg/d,AA-Ag increased to 11.21% ±4.95%(range:2.12% to 28.84%)with 95.00%of the patients with AA-Ag<20%and the rate of the patients with low on-treatment platelet aggregation was 15.00%.Multiple vari-able analysis revealed that aspirin 40 mg/d AA-Ag was significantly influenced by aspirin 100 mg/d AA-Ag,BMI and platelet counts.The rate of gastrointestinal bleeding decreased from 12.00% to 5.00%, and upper gastrointestinal symptoms decreased from 59.00% to 21.00% after the switch in 40 mg/d group.Conclusion:Switching aspirin dosage from 100 mg/d to 40 mg/d reduces the bleeding events and improves upper gastrointestinal symptoms,thus inhibiting platelet aggregation effectively in very elderly patients.

AIM:To explore whether histamine can regulate the expression of early growth response factor-1 (Egr-1) in the cerebral cortex astrocytes.METHODS:Normal wild-type (WT) mice, histidine decarboxylase knockout ( HDC-KO) mice and histamine treated HDC-KO mice were sacrificed for extracting the total RNA of the cerebral cortex. Primary cultured rat cortical astrocytes were treated with histamine at concentrations of 10 -8 , 10 -7 , 10 -6 , 10 -5 or 10 -4 mol/L for 15, 30, 60, 120 or 240 min.H1 or H2 receptor antagonists were pretreated for 15 min before histamine treat-ment.After histamine treatment, the cell total RNA or protein was extracted.The expression of Egr-1 at mRNA and protein levels was determined by real-time PCR and Western blot.RESULTS:The mRNA level of Egr-1 in cerebral cortex of HDC-KO mice was significantly lower than that in WT mice, while exogenous histamine induced the mRNA expression of Egr-1 in HDC-KO mice.In cultured astrocytes, histamine induced the mRNA expression of Egr-1.The maximum increase in the mRNA level of Egr-1 was produced by histamine at concentration of 10 -5 mol/L.In addition, histamine-induced Egr-1 mRNA accumulation peaked at 30 min after commencing stimulation, while histamine significantly increased Egr-1 protein expression at 60 min.Furthermore, histamine-induced Egr-1 expression was inhibited by H1 receptor antagonist but not H2 receptor antagonist.CONCLUSION:Histamine up-regulates the Egr-1 expression in cerebral cortex and cultured astrocytes, which may attribute to H1 receptor activation.

The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests

Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein.Imatinib is the first-line treatment of CML;however,many patients are resistant to this drug.In this study,we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments.GSE24946 was downloaded from the GEO database,which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5).Three drug treatment groups were considered for this study:arsenic trioxide (ATO),AMN107,and ATO+AMN107.Each group had one sample at each time point (3,12,24,and 48 h).Time-series genes with a ratio of standard deviation/average (coefficient of variation) ＞0.15 were screened,and their expression patterns were revealed based on Short Time-series Expression Miner (STEM).Then,the functional enrichment analysis of time-series genes in each group was performed using DAVID,and the genes enriched in the top ten functional categories were extracted to detect their expression patterns.Different time-series genes were identified in the three groups,and most of them were enriched in the ribosome and oxidative phosphorylation pathways.Time-series genes in the three treatment groups had different expression patterns and functions.Time-series genes in the ATO group (e.g.CCNA2 and DAB2)were significantly associated with cell adhesion,those in the AMN107 group were related to cellular carbohydrate metabolic process,while those in the ATO+AMN107 group (e.g.AP2M1) were significantly related to cell proliferation and antigen processing.In imatinib-resistant CML cells,ATO could influence genes related to cell adhesion,AMN107 might affect genes involved in cellular carbohydrate metabolism,and the combination therapy might regulate genes involved in cell proliferation.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult